DNA polymerase ζ generates tandem mutations in immunoglobulin variable regions
Processivity
RNA polymerase III
DNA polymerase II
DNA polymerase mu
DOI:
10.1084/jem.20112234
Publication Date:
2012-05-22T02:51:23Z
AUTHORS (7)
ABSTRACT
Low-fidelity DNA polymerases introduce nucleotide substitutions in immunoglobulin variable regions during somatic hypermutation. Although polymerase (pol) η is the major low-fidelity polymerase, other may also contribute. Existing data are contradictory as to whether pol ζ involved. We reasoned that presence of mask contribution ζ, and therefore we generated mice deficient for heterozygous ζ. The frequency spectra hypermutation was unaltered between Polζ+/− Polη−/− Polζ+/+ clones. However, there a decrease tandem double-base cells compared with cells, suggesting generates mutations. Contiguous mutations consistent biochemical property extend mismatch second mutation. this unique signature implies contributes mutational synthesis vivo. Additionally, on from wild type, Polζ+/−, Polζ−/−, Ung−/−, Msh2−/−, Msh6−/−, Ung−/− Msh2−/− clones suggest function MSH2–MSH6 pathway.
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